tbl 1 physiology: Mouth and Oesophagus

Question 1

Mastification- involves movements of the jaws, actions of teeth and coordinated movements of the tongue and other muscles of the oral cavity.

Functions – to facilitate swallowing by mixing food with saliva, reducing the size of food particles and mixing carbohydrates in food with salivary _____ to initiate carbohydrate digestion

Answer 1

amylase

Question 2

Saliva and salivary glands – salivary glands produce 1 litre of saliva per day – parotid (____ mL/day), sublingual (___ mL/day), submandibular (700 mL/day)
- Salivary glands include parotid gland (mainly ___), sublingual gland (mainly ____) and submandibular gland (mixed)
o Serous cells secrete aqueous fluid composed of water, ions, enzymes (watery secretion)
o Mucus cells secrete mucin glycoproteins for lubrication (viscous secretion)

Answer 2

250; 50; serous; mucous

Question 3

Features of saliva

• tonicity: _____
• pH: resting- pH 7.0
• Na+ and Cl-: ___ than in plasma
• K+ and HCO3-: _____ than in plasma
• Other ions: Ca2+, Mg2+, PO4 3-
• organic contents: proteins (salivary amylase, mucin)

Answer 3

hypotonic, lower, higher

Question 4

Production of saliva
- Initial saliva: _____ cells produce initial saliva composed of water, ions, enzymes and mucus (initial saliva is isotonic)
o Acinar cells also contain zymogen granules produced by mucous cells that store salivary enzymes (e.g. salivary amylase) – secreted into the initial saliva
- Ejection of initial saliva into ducts: ______ cells in the acini contract to eject saliva into the ducts.
- Modification of initial saliva by ducts – NaCl is absorbed and KHCO3 is secreted
o Ductal cells are relatively impermeable to water – net absorption of solute is not balanced by water absorption, and thus final saliva is hypotonic

Answer 4

acinar; myoepithelial

Question 5

Factors affecting nature of saliva
o Effect of flow rate – at high flow rates, the duct has less time to modify initial saliva, so final saliva is ____
§ At slow flow rates, the duct has more time to modify initial saliva, so final saliva is hypotonic
o _______ (hormone from the adrenal gland) promotes sodium absorption and potassium secretion in salivary ducts
- Ductal modification of initial saliva – the net effect is that NaCl is absorbed and KHCO3 is secreted
o As solutes are absorbed but not water, final saliva is hypotonic

Answer 5

isotonic; Aldosterone

Question 6

[Production of saliva]

Luminal side

• Na+ is absorbed in exchange for H+ via the _______
• K+ is secreted into the salivary ductal lumen in exchange for H+ through the _____
• H+ secreted into the lumen via the Na-H exchanger is balanced by the H+ absorbed into the ductal cell via the K-H exchanger– thus no net change of H+
• Cl- is absorbed in exchange for HCO3- via the _______

Basolateral side

• Na+ is pumped into interstitial fluid by _____ in exchange for K+ being pumped into the ductal cell
• Cl- flows passively down its electrochemical gradient into the interstitial fluid through chloride channels

Answer 6

Na-H exchanger; K-H exchanger; anion exchanger; Na-K ATPase

Question 7

Control of salivary secretion

• Sublingual and submandibular glands are innervated by the __________
• Parotid gland is innervated by the ________

Answer 7

facial nerve (CN VII); glossopharyngeal nerve (CN IX)

Question 8

Control of salivary secretion
- Parasympathetic stimulation causes watery secretion and secretion of salivary amylase, but concentration of amylase is low due to a large increase in saliva volume
o Local vasodilation is mediated by _________
o Acetylcholine and cholinergic agents such as neostigmine, organophosphate poisoning,
mushroom poisoning increase salivation
o Anti-cholinergic drugs such as ________ decrease salivation

-Sympathetic stimulation causes vasoconstriction, reduces watery secretion,
increases mucous secretion and increases enzymes in saliva

Answer 8

vasoactive intestinal peptide (VIP); scopolamine

Question 9

Digestive functions of saliva
- Carbohydrate – salivary amylase breaks down starches producing ____, _____, maltose
o Short acting – inactivated by gastric acid once swallowed

• Fats – lingual lipase breaks down triglycerides to generate fatty acids and 1,2- diacylglycerols
  o Long acting – remains active in the stomach and contributes to fat digestion
  in the stomach
• _______ secreted by the salivary glands is required for vitamin B12 absorption – binds to free vitamin B12 in the stomach, protecting it from gastric acid

Answer 9

dextrins; maltotriose; R-binder

Question 10

Oral phase of swallowing

1. Jaws shut and lips close
2. Tongue brings food bolus into midline
3. Tip of tongue presses against ______ and limits the bolus
4. Voluntary contraction of _______ pushes food bolus towards posterior pharyngeal wall

Answer 10

hard palate; mylohyoid muscle

Question 11

Pharyngeal phase of swallowing

• Food bolus enters the pharynx and stimulates sensory endings in the posterior pharyngeal wall, soft palate, and epiglottis
• Afferent signals are sent through cranial nerves – initiates the ________. The deglutition center is located in the medulla in the brain stem

1. Tongue rises, closing ________
2. Soft palate rises, shutting off _______
3. _______ rises and moves forward
4. Anterior wall of esophagus is drawn forward by the hyoid bone
5. Esophageal lumen is pulled open
6. Epiglottis tilts backward to shut off glottis and the vocal cords approximate

Answer 11

deglutition (swallowing) reflex; oropharynx; nasopharynx; Hyoid bone

Question 12

Oesophageal phase of swallowing

1. The upper esophageal sphincter (UES) opens to allow food bolus to enter the esophagus, and then closes
2. The primary peristaltic contraction propels food down the esophagus
3. The lower esophageal sphincter (LES) opens to allow food bolus to enter stomach
4. Receptive relaxation of the stomach accommodates the food bolus that arrive
5. The secondary peristaltic wave triggered by ________ due to food remnants, or by the _________ into the esophagus clears the esophagus of any residual food bolus

Answer 12

esophageal distension; reflux of gastric contents

Question 13

The oesophagus extends from the UES to the LES (7 to 9 inches long)
- Upper Esophageal Sphincter (UES) – 2 to 4 cm long high pressure zone at the upper end of the oesophagus, which is normally closed
o Anterior wall is ________, lateral and posterior walls are composed mainly of the _________ , which is normally contracted at rest
o Upon initiation of swallowing, the cricopharyngeus muscle relaxes in anticipation of the bolus – helps to form part of the pharyngeal peristaltic wave
o Cricopharyngeus muscle is usually not seen on a barium swallow – however, in some individuals a prominent cricopharyngeus is seen as a ________, a smooth, posterior bar or band-like protrusion into the barium column
§ Once the bolus passes the UES into the oesopahgus, the cricopharyngeus contracts closing off the UES thereby preventing reflux – the glottis reopens and breathing resumes

Answer 13

cartilaginous; cricopharyngeus muscle; cricopharyngeal bar

Question 14

Movement of bolus of food down the oesopahgus – food bolus is propelled by peristalsis in the oesophagus
o Movement of bolus is aided by gravity – food travels down oesophagus faster in the standing position
o Peristaltic waves are strong enough to propel food against gravity – swallowing is possible even when a person is standing on his/her head

• Secondary peristaltic waves – originate in the oesopahgus due to continued distention or reflux of gastric contents
  o Helps clear the oesophagus of residual food
  o Mediated by the __________
  o The secondary wave begins at the site of distention above the bolus of food and pushes the bolus down

Answer 14

enteric nervous system

Question 15

Lower Esophageal Sphincter (LES) – opening is mediated by ________ , stimulated by the presence of food
o Vasoactive intestinal peptide (VIP) is released from peptidergic fibers, which relaxes the smooth muscle of the LES
o Receptive relaxation of the stomach – as the LES relaxes, the orad (upper) region of the stomach relaxes to accommodate the food bolus that is entering from the oesophagus

Answer 15

peptidergic fibers in the vagus nerve (CN X)

Question 16

Primary peristaltic contraction – propel food down the oesophagus into the stomach
- PPC begins at the _____ and travels down past the ________ – ensures that the LES relaxes in synchrony with the relaxation of the UES
- The oesophagus is normally collapsed and as one initiates a swallow, the peristaltic wave goes down the oesophagus with time (x-axis)
- Peristalsis – reflex response initiated when the gut wall is stretched, occurs in all parts of the GI tract from the oesopahgus to the rectum
o Primary peristaltic activity can be increased or decreased by the autonomic input to the gut, but its occurrence is independent of extrinsic innervation

Answer 16

UES; LES into the stomach

Question 17

Anatomy of the oesophagus with respect to peristalsis – majority of the oesophagus lies in the thorax
- The resting tone of the oesophagus is 0mmHg, UES is _____and LES is ____
o The UES and LES are tonically active and the oesophagus is normally collapsed under the intrathoracic pressure
- LES is is tonically active, maintaining a resting pressure of 20 mmHg, but it relaxes on swallowing
o Excitatory vagal input contributes to the high-pressure zone, but the principal determinant of LES pressure is the _____________, which can be modified by excitatory and inhibitory signals

Answer 17

50 mm Hg; 20mmHg; intrinsic (myogenic) property of the circular smooth muscle of the sphincter

Question 18

• Arrangement of muscle in oesophagus – the upper third is striated muscle, lower third is smooth muscle, and middle third is a mixture of striated muscle and smooth muscle
• Z-line (squamocolumnar junction) – where ______ epithelium of the oesophagus changes to ______ epithelium of the stomach
  o In Barrett’s oesophagus, squamous epithelium above the Z-line is replaced by (intestinal like) columnar epithelium, a response to prolonged and repeated exposure of the mucosa to acidic refluxed contents from the stomach
  o This is followed by metaplasia – can progress to _________ of the oesophagus
• Gastro-esophageal junction prevents gastric acidic contents from entering the oesophagus
  o If refluxed into the oesopahgus, gastric acidic contents will damage the oesophageal lining (occurs in GERD)

Answer 18

squamous; columnar; adenocarcinoma

Question 19

Control of swallowing
- The oesophagus transports ingested liquids and solids from the oropharynx to the stomach during a swallow and serves as a conduit for expulsion of gastric contents during emesis
- Swallowing reflex is initiated when sensory receptors in the pharynx detect a food bolus
o Afferent signals are sent from the pharynx through cranial nerves ______ to the swallowing centre in the medulla (______. ________)
o Efferent signals are sent from the swallowing centre through cranial nerves _________ to the striated muscle of the pharynx, particularly the cricopharyngeal muscles and upper third of the oesophagus to initiate swallowing

Answer 19

V, IX and X; nucleus of tractus solitarius, nucleus ambiguous; V, VII and XII

Question 20

Control of LES opening – the balance between the excitatory and inhibitory pathways determines whether the LES remains open or closed.
o Excitatory Pathway – pre-ganglionic nerve fibres carried in the ______ and postganglionic nerve fibres in the esophageal wall
§ Both sets of fibres are cholinergic – preganglionic nerve fibres release acetylcholine (ACh) and post-ganglionic nerve fibres release _________
§ These neurotransmitters contract oesophageal smooth muscle and tighten the lower esophageal sphincter (LES)
o Inhibitory Pathway – pre-ganglionic cholinergic nerve fibres carried in the vagus Nerve (CN X) and post-ganglionic nitrergic nerve fibres in the esophageal wall constitute the inhibitory pathway
§ Pre-ganglionic nerve fibres release acetylcholine (ACh), and postganglionic
nerve fibres release _______________
§ These neurotransmitters relax oesophageal smooth muscle and relax the LES

Answer 20

vagus Nerve (CN X); 
ACh and Substance P; 
nitric acid (NO), vasoactive intestinal peptide (VIP) and ATP

Question 21

Pathology of swallowing – achalasia cardia
o Reduction or absence of nitric oxide (NO)-producing post-ganglionic nerve fibres while excitatory pathways are intact
o LES does not relax properly resulting in dysphagia – difficulty in swallowing
o Patients complain of food stuck in the chest after swallowing (worse for solids than liquids), and also regurgitation
o Manometric studies on these patients shows the LES has a _______ at rest and fails to relax on swallowing
o Radiological barium swallow studies reveal a ______ appearance due to the smooth tapering of the lower oesophagus leading to a closed LES

Answer 21

high pressure; “birds beak”

Question 22

Gastro-oesophageal barrier and GERD
- Gastro-esophageal junction: separates the neutral pH of the oesophagus from the acidic pH of the stomach
- Intrinsic sphincter – lower esophageal sphincter (LES) is only vaguely identifiable anatomically as a slight thickening of the muscle coat of the esophageal wall
o 5 cm long with 3 cm lying below the diaphragm in the abdomen and 2 cm lies above the diaphragm in the thorax
o Tonically active – resting pressure of 20 mmHg, but relaxes on swallowing
o Although excitatory vagal input contributes to the high-pressure zone, the principal determinant of LES pressure is the intrinsic (myogenic) property of the circular smooth muscle of the sphincter – _____________ released from inhibitory postganglionic neurons relax the lower esophageal sphincter

• Extrinsic sphincter
  o Oesophageal compression by diaphragm – skeletal muscle fibres in the ______ of the diaphragm compress the oesophagus as it passes through the
  hiatus in the diaphragm
  o _______ formed between the cardia of the stomach and the distal oesophagus – functions as a flap at the gastro-esophageal junction
• Intra-abdominal pressure – a small portion of the oesophagus lies in the abdomen (the majority lies in the thorax)
  o Compresses the walls of the intra-abdominal segment of the oesophagus
  o Healthy people do not have reflux into the oesophagus during straining when the abdominal muscles are contracted

Answer 22

vasoactive intestinal peptide (VIP), nitric oxide and ATP; right crus; Angle of His

Question 23

• Reflux in healthy people – reflux of acidic gastric contents into the oesophagus can occur in healthy people
  o Refluxed material initiates secondary peristalsis, which efficiently clears the oesophagus of the contents
  o The swallowing of alkaline saliva neutralizes residual acid – symptoms do not occur
• Gastro-Esophageal disease occurs when the ________ is exposed to acidic gastric contents for prolonged periods
  o Any patient with heartburn or acid regurgitation for more than once per week should be considered to have gastro-esophageal reflux disease unless otherwise proven

Answer 23

esophageal mucosa

Question 24

Causes of GERD:
- abnormalities of the lower esophageal sphincter: Normally, the sphincter is tonically contracted, relaxing only during swallowing. Reduced lower esophageal sphincter tone permits reflux when ______ rises.

• Delayed esophageal clearance: Defective esophageal peristaltic activity is commonly found in patients who have ______. Poor esophageal clearance leads to increased ______
• Defective gastric emptying: Delayed gastric emptying – impaired transit of food from the stomach to the duodenum ________ is the most common cause of gastroparesis – damage to neurons that control gastric emptying
• environmental factors: caffeine, fatty foods, acidic food, smoking, late night meals and alcohol
• increased abdominal pressure in Pregnancy: Enlarged uterus pushes the stomach up and pushes the abdominal part of the oesophagus into the thorax, increasing the chance of reflux of gastric contents into the oesophagus. High _____ level in pregnancy reduces the tone of the lower esophageal sphincter, contributing to the enhanced likelihood of reflux during pregnancy

Answer 24

intra-abdominal pressure; esophagitis; acid exposure time; Diabetes mellitus; progesterone

Question 25

Emesis- protective reflexes that rid stomach and intestine of toxic substances and prevent further ingestion

Pre-ejection: stomach relaxes and _____ occurs in the intestine

Retching: ________ muscles contract against a closed glottis while UES remains closed. LES is open – gastric contents return to the stomach when retch is over

Ejection:

• Breath is held in mid-inspiration
• ______ closes to prevent aspiration of vomitus into respiratory system
• Hyoid bone moves _______ causing UES to open. Reverse peristalsis in the intestine propels intestinal contents as the stomach relaxes and the pyloric sphincter opens to accept intestinal contents Intense contraction of abdominal muscles increases abdominal pressure, which ejects the vomitus into the oesophagus and out of the mouth

Answer 25

retroperistalsis; Abdominal, intercostal and diaphragmatic;

Glottis; upwards and forwards

Question 26

What does MAGIC PAD stands for causes of emesis?

Answer 26

Metabolic, Acute abdomen, Gastroduodenal, Infections, Central Nervous system, Psychogenic/ Pregnancy, Alcholism, Drugs

Question 27

What metabolic diseases can cause Emesis?

Answer 27

Diabetic ketoacidosis, Addison’s disease (adrenal insufficiency), uremia
(renal failure)

Question 28

What acute abdomen disease can cause emesis?

Answer 28

Appendicitis, cholecystitis, pancreatitis, intestinal obstruction

Question 29

Gastroduodnal causes of emesis

• Peptic ulcer disease, gastric cancer
• Gastroparesis (syndrome characterized by delayed gastric emptying, resulting in impaired transit of food from the stomach to the _____ in the absence of mechanical obstruction)
• Diabetes mellitus is the most common cause of gastroparesis

Answer 29

duodenum

Question 30

What drugs can cause emesis?

• NSAIDs (non-steroidal anti-inflammatory drugs, e.g.
  ibuprofen) , opiates;_____, some antibiotics; cancer chemotherapeutic agents (e.g. Cisplatin, ______, Methotrexate and Doxorubicin), post-radiation therapy

Answer 30

digoxin; Cyclophosphamide

Question 31

Haematemesis (vomiting of blood) – most common gastrointestinal emergency
o Vomit may be red with clots when bleeding is profuse, or coffee grounds-like when less severe
o Causes – bleeding esophageal varices, ________ (lacerations of the gastro-esophageal lining due to repeated retching, which extend to submucosal blood vessels causing profound bleeding), bleeding gastric or duodenal ulcer, bleeding gastric cancer lesion, gastric erosions due to alcoholism or NSAIDs

Answer 31

Mallory Weiss tear

Question 32

Afferent pathways of emesis

• touch receptors in throat: Signals from the back of the throat (gag reflex) are sent through _________ to the vomiting center
• Labrynthine receptors: Motion sickness – stimuli from the ______ (labyrinthine receptors in inner ear) are relayed to the vestibular nuclei in the brain stem and from there via the chemoreceptor trigger zone to the vomiting center
• Mechanoreceptors and chemoreceptors in stomach and duodenum: triggered by toxins, food poisoning, food allergens, drugs etc. Signals are sent via the vagus nerve to the
  vomiting center.
• Chemoreceptor Trigger Zone: Nausea and vomiting due to cancer chemotherapy, radiation
  therapy, and uremia (renal failure) develops because of the formation of endogenous emetic substances that act on the chemoreceptor trigger zone, which lies in the brain stem near the vomiting center, and relay signals to the vomiting center.

• Raised ______ stimulates the vomiting center directly causing projectile
vomiting – forceful and rapid ejection of vomitus.

• Psychic stimuli: foul smell, a grotesque experience, a sickening sight – these stimuli travel from the ______ to the vomiting center.

Answer 32

CN IX (glossopharyngeal nerve) and X (Vagus nerve); vestibular apparatus; intracranial pressure; limbic system

Question 33

Efferent pathways: Efferent signals are relayed via cranial nerves ________________to the abdominal and respiratory muscles, esophageal sphincters and esophageal muscles. Vomiting center lies in the medulla close to the swallowing center within the

Answer 33

V (trigeminal nerve), VII (facial nerve), IX (glossopharyngeal nerve), X (vagus nerve) and Xii (hypoglossal nerve)

Question 34

Muscarinic M1 receptor antagonists
• Anti-cholinergic agents (_______) used as transdermal patches for the control of motion sickness.
• Side effects: dry mouth, throat and nasal passages, which can progress in over-dose cases to impaired speech, thirst, blurred vision and sensitivity to light, constipation, difficulty in urination and tachycardia

Answer 34

scopolamine

Question 35

Histamine H1 receptor antagonists
• Antihistamines _______ (Phenergan, Avomine), _______ (Dramamine), _______ (Benadryl) and ______ (Marezine) are effective for the control of nausea and vomiting related to motion sickness and vestibular defects. They might be useful for controlling post- operative vomiting.
• Side effects: sedation

Answer 35

promethazine; dimenhydrinate; diphenhydramine; cyclizine

Question 36

Neurokinin 1 (NK1) receptor antagonists
• Aprepitant and Fosaprepitant cross the \_\_\_\_\_\_\_\_\_ and act on NK1 receptors at the vomiting center and in the chemoreceptor trigger zone. Used to treat cancer chemotherapy-induced nausea and vomiting.

Answer 36

blood-brain-barrier

Question 37

Serotonin 5-HT3 receptor antagonists
• Ondansetron, Granisetron, Dolasetron, Alosteron, Palonsetron are blockers of Serotonin 5-HT3Rs found in the ______________
• Side effects: They may cause constipation or diarrhea and headache. Small but statistically prolongation of
QT interval, most pronounced with dolasetron.

Answer 37

stomach and duodenum, and also in the vomiting center and chemical trigger zone.

Question 38

Centrally acting dopamine D2R antagonists:
• Phenothiazines, _______ (Compazine, Stemetil) and chlorpromazine (Thorazine, Largactil) target dopamine D2Rs in the chemoreceptor trigger zone. Metoclopramide (Reglan), a blocker of D2Rs, is useful for controlling cancer chemotherapy-induced nausea and vomiting.
• Side effect: Metoclopramide can act on brain nigrostriatal pathways to induce ______________ , for example tardive dyskinesia (involuntary, repetitive body movements with belated onset)

Answer 38

prochlorperazine; extrapyramidal motor dysfunction

Question 39

Cannabinoid receptor agonists:
• The cannabinoid CB1 receptor is expressed in neurons around the vomiting center. The cannabinoid ______ (Marinol) acts on the CB1 receptor. It is effective against mild or moderately emetogenic cancer chemotherapeutic regimens.
• Side effects: Euphoria, dysphoria (feeling unwell or unhappy), sedation, hallucinations, dry mouth, increased
appetite, and autonomic effects (tachycardia, conjunctival injection, orthostatic hypotension). Dronabinol
should be prescribed with great caution to persons with a history of substance abuse.

Answer 39

Dronabinol

Question 40

Treatment of Motion Sickness

1. ___________ are effective for the control of nausea and vomiting related to motion sickness.
2. M1 receptor antagonists can also be used for motion sickness

Answer 40

H1 receptor antagonists

Question 41

Moderate to high emetogenic potential

• chemotheurapeutic agent: Cisplatin, Cyclophosphamide, Methotrexate, Doxorubicin
• treatment recommendations: ???

Answer 41

5HT3 receptor antagonists, NK1 receptor inhibitor,

Dexamethasone (steroid).

Question 42

low emetogenic potential

• chemotherapeutic agent: Hydroxyurea, Etoposide, Vinblastine, Bleomycin, Chlorambucil
• treatment recommendation: ???

Answer 42

Centrally acting D2 receptor antagonist (Metoclopramide or Prochlorperazine), Histamine H1 receptor antagonist (Diphenhydramine).

Question 43

Treatment of high and moderate emetic risk cancer chemotherapy, National Comprehensive Cancer Network (USA) guideline (more in Clinical Section)
• Triple therapy consisting of: (i) 5-HT3R antagonist (dolasetron or granisetron or ondansetron or palonosetron); (ii) steroid (dexamethasone); (iii) NK1 receptor antagonist (aprepitant or fosaprepitant).
• Adjuvant therapy: (i) ________ are helpful in reducing anxiety and the anticipatory component of nausea and vomiting. (ii) ______:
reduces heartburn.

Answer 43

Benzodiazepines: Lorazepam and alprazolam; Proton pump inhibitors

Question 44

Treatment of low and minimal emetic risk cancer chemotherapy, NCCN guideline
• Therapy: Metoclopramide or prochlorperazine (D2R antagonists) with or without diphenhydramine (Benadryl; anti-histamine H1 receptor antagonist); or _________; or (D2R antagonist, Compazine, Stemetil)
• Adjuvant therapy: adjuvant benzodiazepine and proton pump inhibitor.

Answer 44

steroid (Dexamethasone)